Novel Compounds from Sycamore Leaves for the Treatment of MRSA

DESCRIPTION provided by applicant Methicillin resistant staphylococcus aureus MRSA is a serious pathogen that can cause patient mortality and extend hospital stays resulting in higher health care costs Currently over of staph cases around the world are caused by MRSA In recent years MRSA has evolved into several resistant strains that can resist to multiple antibiotics such as penicillin vancomycin tetracycline and erythromycin For this reason they are sometimes called andquot superbugs andquot In recent years these andquot superbugsandquot have become a serious threat to public health Because of the increasing presence of MRSA related infections especially in hospitals there are urgent needs for effective and novel antibiotic therapies In a preliminary study we have isolated a novel compound kaempferol O alpha L andquot andquot di p coumaroyl rhamnoside KCR from the American sycamore Platanus occidentalis that were active against MRSA and VRSA vancomycin resistant staphylococcus aureus in vitro and in vivo The sycamore materials have been classified by the USDA as generally regarded as safe GRAS because of extensive human contact and use of this plant in traditional folk medicines and paper industry among others Active metabolites of these anti MRSA compounds likely possess a distinct mechanism of action as they do not show cross resistance or structural homology with established antibiotics In this proposal we plan to furthe investigate these highly selective anti MRSA KCR platanosides including the maximum tolerated dose MTD therapeutic efficacy pharmacokinetics PK mechanism of action and in vivo toxicity using animal model and microbiological techniques This project clearly has the potential to generate a first in class new antibiotic with a novel mechanism of action and provides a unique opportunity for US economic development In addition the success of this project will address the limitations of current therapies for the control of MRSA and other antibiotic resistant staph infections such as VRSA PUBLIC HEALTH RELEVANCE MRSA stands for methicillin resistant staphylococcus aureus which is a serious drug resistant pathogen that causes patient mortality extend hospital stays and higher health care costs Statistical data suggest that as many as people per year have died from MRSA in the U S In recent years MRSA has evolved into several resistant strains that can resist to multiple antibiotics such as penicillin vancomycin tetracycline and erythromycin For this reason they are sometimes called andquot superbugs andquot In recent years these andquot superbugsandquot have become a serious threat to public health Because of the increasing presence of MRSA related infections there are urgent needs for effective and novel antibiotic therapies In this project we plan to investigate novel leaf compound known as KCR from American sycamore that exhibit potent anti MRSA activity in a preliminary study We propose to further study the therapeutic effects and the biological properties of the extracts using animal model and modern microbiological techniques The success of this project will generate a first in class new antibiotic for treating drug resistant infections This project also will provide a unique opportunity for US economic development